DNA multiallelic systems reveal gene/longevity associations not detected by diallelic systems. The APOB locus

To identify possible genetic factors affecting human longevity we compared allele pools at two candidate loci for longevity between a sample of 143 centenarians (S) and a control sample of 158 individuals (C). The candidate loci were APOB and TPO, which code for apolipoprotein B and thyroid peroxidase, respectively. Both restriction fragment length (RFL) (XbaI2488 and EcoRI4154) and variable number of tandem repeat (VNTR) (3'APOB-VNTR) polymorphisms were analysed at the APOB locus; the TPO-VNTR polymorphism (intron 10) was analysed at the TPO locus. The main result of the investigation was that there is an association between the APOB locus and longevity that is revealed only when multiallelic polymorphisms are considered. In particular: (i) the frequency of 3'APOB-VNTR alleles with fewer than 35 repeats is significantly lower in cases than in controls; (ii) the linkage disequilibrium between the XbaI-RFLP and the EcoRI-RFLP is significantly different from 0 in cases but not in controls; (iii) the EcoRI-RFLP and XbaI-RFLP allele frequencies do not discriminate between cases and controls. The differences observed between case and control allele pools are specific to the APOB locus, since no significant difference was observed at the TPO locus.